Multiple Concomitant Medications Research Articles

Deprescribing in an outpatient medical clinic at a tertiary care hospital in Sri Lanka

Introduction: Use of multiple concomitant medications or ‘polypharmacy’ is linked to decreased medication adherence, adverse drug reactions and increased financial burden on patients and the economy. Deprescribing by experienced healthcare personnel can ensure safe and effective use of medications. Many medications, prescribed during hospital stay or at clinic level are continued for unnecessarily long periods, highlighting the necessity for deprescribing. The objectives of this audit were to identify and deprescribe inappropriate medications in patients, identify their comorbidities and explore reasons for the inappropriate medication use.Methods: This deprescribing audit was conducted by systematic sampling in selected adult patients >18 years, attending a medical clinic at National Hospital, Kandy over one month. The audit standard was the American Academy of Family Physicians (AAFP) ‘5-step process in deprescribing’. Our study was based only on the first 3 steps of the AAFP deprescribing process.Results: Out of a total of 402 patients, deprescribing was carried out in 135 (33.58%). In this deprescribed group, 59.3% of patients were female and the mean age was 62.3 (±10.9) years. Furthermore, of the deprescribed patients, 52.6% had hypertension, 44.4% had ischaemic heart disease, and 34.1% had diabetes mellitus. The most deprescribed medication was antiplatelets (37.8%), followed by analgesics (24.4%) and diuretics (20%). A clear indication for using the drug was lacking in 68.9%, while 31.1% of patients continued taking the medication for longer than recommended. Conclusions: In this audit, over one third of patients underwent deprescribing. It provides just a glimpse of the broader issue of inappropriate polypharmacy and the necessity of deprescribing. Future research involving multiple centres is recommended to enhance understanding of medication patterns necessitating deprescribing.

Current Trends, Challenges for Research, and Therapeutic Perspectives in Nutritional Psychiatry

"Nutritional interventions in the field of psychiatry have been explored more intensively in the last two decades, but definitive conclusions based on the retrieved data in the literature about the efficacy of this therapeutic approach are difficult to formulate. This observation has multiple explanations, e.g., these therapeutic interventions are very heterogenous, cohort studies usually enroll different psychiatric populations or healthy subjects with minor psychiatric symptoms, nutritional supplements or special diets are commonly recommended as add-ons to the pharmacological interventions (thus making it difficult to differentiate the impact of each therapy on the outcomes), placebo-controlled randomized studies are still very few, etc. Therefore, a narrative review focused on the main challenges reported during the research in the field of nutritional psychiatry (NP) may be useful for clinicians interested in strategies to augment the efficacy of pharmacological treatments or to find new solutions with low risk of adverse events in patients with organic comorbidities or multiple concomitant medications. Data about the efficacy and tolerability of nutritional interventions explored for psychiatric disorders were searched in four electronic databases (PubMed, Cochrane, Clarivate/Web of Science, and EMBASE). Omega-3 polyunsaturated fatty acids supplementation, healthy diet interventions, folate and vitamin B12, S-adenosyl-L-methionine, N-acetyl cysteine, vitamin B1 and B6, vitamin D, minerals, psychobiotics, inositol, and herbal products were the main interventions identified, and their demonstrated efficacy was quite heterogenous, while their tolerability and safety were good. Therefore, NP is a domain of research that may benefit from more good-quality and longer-duration trials, in order to verify the effectiveness of such augmentation strategies to the already validated treatments."

Vulnerability assessment and decision-making in older patients with head and neck squamous cell carcinomas planned for chemoradiation: Experience from a tertiary care cancer centre in India.

e24028 Background: Radical intent treatment in older patients with head and neck squamous cell carcinomas (HNSCC) is complicated by several factors such as comorbidities and multiple concomitant medications. Assessing vulnerabilities in various domains may enable decision-making. Methods: Patients aged over 60 years with locally advanced HNSCC planned for chemoradiation seen at the geriatric clinic in Tata Memorial Hospital, Mumbai, from June 2018 to December 2022 were identified from the clinic database. Demographic characteristics, treatment details, toxicity and outcome data were retrieved from our hospital electronic medical records. Results: Between June 2018 and December 2022, 87 patients with HNSCC planned for chemoradiation after multimodality joint clinic discussion underwent geriatric assessment (GA) at our clinic. 18 patients (20.6%) underwent radiotherapy alone after being deemed unfit for concurrent chemotherapy, and 50 patients (57.4%) ultimately received concurrent chemoradiation. 15 patients (30%) were vulnerable in the domain of function and falls, 21 (42%) in comorbidities, 3 (6%) in psychological, 1 (2%) in cognition, 6 (12%) each in polypharmacy, nutrition, and social domains, and 8 (16%) in the domain of fatigue. 41 patients (82%) were fit, with 2 or fewer vulnerabilities on GA, and 9 patients (18%) were frail, with 3 or more vulnerabilities. Decision on chemotherapy regimen was made after GA results in 36 patients (72%). In 8 patients (16%), the tentative chemotherapy regimen was changed as per the GA results. Common regimens used were cisplatin 40mg/m2 weekly (28%), nimotuzumab (22%), cisplatin 100mg/m2 3 weekly (10%), docetaxel (8%), and carboplatin alone (6%). The median Cancer Aging and Research Group (CARG) risk score was 6, corresponding to a 44% predicted risk of grade 3 or higher toxicities from a combination chemotherapy regimen. 34% (n = 17) patients developed grade 3 or 4 toxicities, most commonly mucositis (14%) and neutropenia (12%). Toxicity led to dose delay in 9 patients (18%), and discontinuation in 10 patients (20%). Median progression-free survival (PFS) was 18.0 months, (95% CI: 0.9-19.0 months) and median overall survival (OS) was 31 months (95% CI: 4.0-57.9 months). On Cox regression analysis, factors significantly associated with poorer PFS were vulnerabilities in the domain of nutrition (p = 0.04) and comorbidities (p = 0.03), lower G8 score (p = 0.021), and higher CARG score (p = 0.006), and for poorer OS were comorbidities (p = 0.04) and higher CARG score (p = 0.01). Conclusions: Geriatric assessment aids decision-making in older patients with locally advanced head and neck cancers warranting chemoradiation. Vulnerabilities in geriatric domains have survival implications, and identification may help improve outcomes. Clinical trial information: CTRI/2020/04/024675 .

Efficacy and safety of vortioxetine in treatment of patients with major depressive disorder and common co-morbid physical illness

BackgroundThe multimodal antidepressant vortioxetine is effective in reducing somatic symptoms in patients with major depressive disorder (MDD), but little is known about its effects in reducing depressive symptoms in patients with common comorbid physical illnesses. MethodsThis was a pooled analysis of 13 randomized, placebo-controlled trials which evaluated the efficacy (using the Montgomery–Åsberg Depression Rating Scale [MADRS]) and safety of vortioxetine (5-20 mg/day) in adult patients with MDD. We evaluated stable somatic comorbid conditions that were verified by a diagnosis and had sufficient database representation. ResultsOf the 5982 patients included in the database, 963 (16.1%) patients had a diagnosis of cardiovascular disease, 152 (2.5%) had diabetes mellitus and 26 (0.4%) had chronic obstructive pulmonary disorder (COPD). At Week 8, adjusted mean[95%CI] treatment differences (vortioxetine vs. placebo) on MADRS total scores were −2.7[−4.2, −1.3] (p = 0.0002) points for the cardiovascular disease, −4.0[−7.7, −0.4] (p = 0.03) for the diabetes, and −6.2[−21.3, 8.9] (p = 0.36) for the COPD groups. The rate and pattern of adverse events were similar across the sub-groups with comorbidities and was consistent with that expected for vortioxetine treatment. LimitationsThe primary studies were not designed to investigate the relationship between vortioxetine and comorbidities, nor were the post hoc analyses powered to detect group differences. ConclusionsPatients with MDD and comorbid cardiovascular disease or diabetes respond to vortioxetine in a similar way to the broader MDD population. Vortioxetine was generally safe and well tolerated and without unexpected adverse events in these subpopulations, most of whom are taking multiple concomitant medications.

Clinical Opportunities for Germline Pharmacogenetics and Management of Drug-Drug Interactions in Patients With Advanced Solid Cancers.

Precision medicine approaches, including germline pharmacogenetics (PGx) and management of drug-drug interactions (DDIs), are likely to benefit patients with advanced cancer who are frequently prescribed multiple concomitant medications to treat cancer and associated conditions. Our objective was to assess the potential opportunities for PGx and DDI management within a cohort of adults with advanced cancer. Medication data were collected from the electronic health records for 481 subjects since their first cancer diagnosis. All subjects were genotyped for variants with clinically actionable recommendations in Clinical Pharmacogenetics Implementation Consortium guidelines for 13 pharmacogenes. DDIs were defined as concomitant prescription of strong inhibitors or inducers with sensitive substrates of the same drug-metabolizing enzyme and were assessed for six major cytochrome P450 (CYP) enzymes. Approximately 60% of subjects were prescribed at least one medication with Clinical Pharmacogenetics Implementation Consortium recommendations, and approximately 14% of subjects had an instance for actionable PGx, defined as a prescription for a drug in a subject with an actionable genotype. The overall subject-level prevalence of DDIs and serious DDIs were 50.3% and 34.8%, respectively. Serious DDIs were most common for CYP3A, CYP2D6, and CYP2C19, occurring in 24.9%, 16.8%, and 11.7% of subjects, respectively. When assessing PGx and DDIs together, approximately 40% of subjects had at least one opportunity for a precision medicine-based intervention and approximately 98% of subjects had an actionable phenotype for at least one CYP enzyme. Our findings demonstrate numerous clinical opportunities for germline PGx and DDI management in adults with advanced cancer.

Evaluating the Potential Statin-Drug Interactions among Older Patients with Chronic Diseases in Sana’a City, Yemen

Background: Individuals aged more than 55 years may be more likely to experience chronic diseases and are treated with multiple concomitant medications. This may result in drug-drug interactions (DDIs) that are often not considered in clinical practice settings. Statins are effective in older patients with or at risk for cardiovascular disease (CVD) and are prescribed on a regular basis for a long term and may undergo DDIs. The risk of DDIs varies among statins, and prevalence and severity levels of statin-drug interactions are important in older patients with chronic conditions on concomitant drugs. Objectives: To evaluate the prevalence and severity of the potential statin-drug interactions among older adult patients (55 years or older) who have received statin therapy at hospital discharge for a period of 18 months from January 2021 to June 2022 in Sana’a city. Methods: This cross-sectional study was conducted in a hospital in Sana’a city from January 2021 to June 2022. Data collection was from the electronic medical records (covering demographic, clinical, and drug-therapy-related variables). The format was also filled with; BP, Sr.cr, HbA1c, HR, Total cholesterol, TG, LDL, HDL, AST, and ALT values for each patient. Drug interactions were identified using both Medscape and Lexicomp software. Results: Out of 200 patients, there were 175 (87.5%) individuals had a total of 865 clinically significant drug-drug interactions. specifically speaking, 55 (27.5%) individuals had a total of 72 clinically significant statin-drug interactions. 57 (79.1%) of which were category C, 14 (19.44%) of which were category D, and only 1 (1.39%) category X statin-drug interaction. There was also an association between advanced age, co-morbidities, and concomitant drugs with the presence of statin-drug interaction. Conclusion: It can be concluded from this study, that statin medications have a significant prevalence among elderlies due to the presence of multiple co-morbidities and subsequently the concomitant use of multiple medications. It was also noticed that category C statin-drug interactions were the most common and then followed by category D statin-drug interactions.

Favorable Outcomes for Patients Treated with U2 with Co-Morbidities or Concomitant Medications: A Retrospective Analysis of Unity-CLL Phase 3 Trial

Favorable Outcomes for Patients Treated with U2 with Co-Morbidities or Concomitant Medications: A Retrospective Analysis of Unity-CLL Phase 3 Trial

10 powodów, dla których warto wybrać pantoprazol u pacjentów z polipragmazją

Proton pump inhibitors are the most effective therapy for all the acid-dependent diseases. Pantoprazole has been used since 1997 and it has a precise and predictable profile of activity. Pantoprazole maintains its stability in higher gastric pH with concomittant antiacids. Its constant bioavaibility and maximal blood levels are achieved after the first dose. Pantoprazole is approved for a variety of gastric acid-related diseases: gastroesophageal reflux disease, peptic ulcer disease, Helicobacter pylori eradication, functional dyspepsia, NSAID-induced gastropathy treatment and prevention, and Zollinger-Ellison syndrome. Pantoprazole has been shown to have no significant interactions with other medications: especially important with antiplatelet drugs (clopidogrel), but also antipyrine, carbamazepine, ciclosporin, clarithromycin, diclofenac, naproxen, nifedipine, oral contraceptives, tacrolimus, theophylline, warfarin, and also ethanol. Pantoprazole is the very good choice particularly in patients taking multiple concomitant medications – such as the elderly or those receiving drugs with a narrow therapeutic window. Even in the long-term therapy, pantoprazole seems to be well tolerated with no identified safety concerns.

Effects of SGLT2 inhibitors on eGFR in type 2 diabetic patients\u2014the role of antidiabetic and antihypertensive medications

Recent randomized trials demonstrating the beneficial effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in type 2 diabetes suggest that early reductions in eGFR upon initiation of SGLT2i therapy are associated with improved renal outcomes. Multiple concomitant medications, including antidiabetic and antihypertensive agents, are commonly used, however, which may modify the renal hemodynamic action of SGLT2is. Here we found that background treatment with metformin diminished the SGLT2i-induced reductions in eGFR after 3 months of SGLT2i therapy in patients with type 2 diabetes and hypertension (−2.29 ± 0.90 vs −5.85 ± 1.27 mL/min/1.73 m2 for metformin users (n = 126) and nonusers (n = 97), respectively). Other antidiabetic agents (DPP4 inhibitors, sulfonylureas and insulin) had no effect on the eGFR response to SGLT2is. Antihypertensive drugs, including calcium channel blockers (CCBs) and β blockers, did not affect the SGLT2i-induced changes in eGFR, whereas renin-angiotensin system inhibitors (RASis) tended to enhance this response (p = 0.059). Next, we evaluated the interaction between metformin and RASis in the eGFR responses to SGLT2is. Under no background treatment with RASis, metformin abrogated the eGFR response to SGLT2is, but this response was preserved when RASis had been given along with metformin (decreases of 0.75 ± 1.28 vs. 4.60 ± 1.15 mL/min/1.73 m2 in eGFR, p = 0.028). No interaction between metformin and insulin or between metformin and DPP4 inhibitors was observed. In conclusion, metformin blunts the SGLT2i-induced decrease in eGFR, but coadministration of RASis ameliorates this response. Furthermore, the inability of CCBs to modify the SGLT2i-induced reduction in eGFR suggests that the SGLT2i-induced renal microvascular action is mediated predominantly by postglomerular vasodilation rather than preglomerular vasoconstriction.

Drug-drug interactions of newly approved small molecule inhibitors for acute myeloid leukemia.

Several small molecule inhibitors (SMIs) have been recently approved for AML patients. These targeted therapies could be more tolerable than classical antineoplastics, but potential drug-drug interactions (DDI) are relatively frequent. Underestimation or lack of appropriate awareness and management of DDIs with SMIs can jeopardize therapeutic success in AML patients, which often require multiple concomitant medications in the context of prior comorbidities or for the prevention and treatment of infectious and other complications. In this systematic review, we analyze DDIs of glasdegib, venetoclax, midostaurin, quizartinib, gilteritinib, enasidenib, and ivosidenib. CYP3A4 is the main enzyme responsible for SMIs metabolism, and strong CYP3A4 inhibitors, such azoles, could increase drug exposure and toxicity; therefore dose adjustments (venetoclax, quizartinib, and ivosidenib) or alternative therapies or close monitoring (glasdegib, midostaurin, and gilteritinib) are recommended. Besides, coadministration of strong CYP3A4 inducers with SMIs should be avoided due to potential decrease of efficacy. Regarding tolerability, QTc prolongation is frequently observed for most of approved SMIs, and drugs with a potential to prolong the QTc interval and CYP3A4 inhibitors should be avoided and replaced by alternative treatments. In this study, we critically assess the DDIs of SMIs, and we summarize best management options for these new drugs and concomitant medications.

Infections in elderly intensive care unit patients

The elderly population is increasing in the developed world, therefore elderlies account for a considerable proportion of intensive care unit (ICU) admissions. A precise threshold for “elderly” is a matter of debate. The process of ageing is associated with physiological and functional alterations of the human body and organs that render elderly people vulnerable to infections. As a result of dysfunction of specific parts of immune response called immunosenescence, elderly patients may be threatened by severe infections. Chronic low-grade inflammation, termed inflammaging, is another contributor. In addition to these, comorbidities associated with increasing age, such as diabetes mellitus and immunosuppressive conditions pose an additive risk for infections and in some studies they were associated with increased mortality. Epidemiology of ICU infections may differ in elderlies, compared to other adults. Infections tend to be less microbiologically confirmed and site of infection may be obscure on presentation. The identified pathogens are frequently Gram-negative and particularly Enterobacteriaceae exhibiting a multidrug-resistant (MDR) phenotype. Multiple antibiotic prescriptions in this age-group, specific comorbidities (such as bronchiectasis or chronic obstructive pulmonary disease), residence in long term care facilities and frequent hospitalisations, are among others recognized risk factors for MDR infections. Data from two large European databases show that intra-abdominal infections are predominant among ICU infections in the elderly and Candida spp infections rank second, after Enterobacteriaceae. Age may pose important implications in treatment decisions. Organ derangements, physiological changes caused by increasing age and multiple concomitant medications call clinicians for vigilance about adverse events and toxicity. Despite all the above, elderlies in the ICU did not exhibit worse outcomes compared to younger counterparts in a straightforward manner. Studies however are heterogenous and most of them are single centers. As age is a continuous process, only analysis performed in subgroups of 65–74 (young-old elderlies), 75–84 (old elderlies) and >85 (old-old or oldest old elderlies) provides a better depiction of ICU outcomes. Most studies have shown a worse ICU outcome for the group of oldest-old elderlies, compared with young adults and elderlies in the range of 65 to 84 years of age. These data indicate that age per se may not represent a barrier in decisions concerning ICU admission and triage has to be done on an individual basis. However, epidemiological particularities of this age group should be taken into account in the selection of early and appropriate antimicrobial treatment, which will optimize patients’ outcomes.

Direct oral anticoagulants use in elderly patients with non valvular atrial fibrillation: state of evidence.

Non-valvular atrial fibrillation (NVAF) increases the risk of stroke by three- to five-fold, especially in elderly patients, creating a huge burden on medical system as well as a negative impact on patients' lives. Balancing efficacy and bleeding risk is a challenge when considering anticoagulation therapy in elderly patients, because of their frequent high risk of both stroke and bleeding. Real world data reveal the underuse of anticoagulation in the elderly, especially due to physicians' fear of bleeding, often neglecting the thromboembolic risk. Care of elderly patients with NVAF is often complicated by factors including adherence, cognitive impairment, health literacy, risk of falling, adverse effects, involvement of caregivers, and patient-physician relationship. Therefore, shared decision making and conversations between clinicians and patients are crucial. In addition, elderly patients often suffer from multiple comorbidities, requiring multiple concomitant medications, with an increased risk of drug interactions. Four non-vitamin K antagonist oral anticoagulants, the so-called direct oral anticoagulants (DOACs) - dabigatran, rivaroxaban, apixaban and edoxaban - have been approved for reducing the risk of stroke and systemic embolism in patients with NVAF. Clinical trials and real-world data show the advantages of this class of drugs compared to conventional anticoagulation in the treatment of elderly patients with NVAF and identify subgroups of older patients who may be more suitable candidates for particular agents. However, there are conflicting opinions on the absolute benefit of DOACs use in elderly patients. A key factor to consider is that elderly patients frequently suffer from renal impairment and therefore dose adjustments according to creatinine clearance are mandatory for DOACs. As each DOAC comes with its own unique advantages and safety profile, a personalized case by case approach should be adopted to decide on the appropriate anticoagulation regimen for elderly patients after weighing the overall risks and benefits of therapy.

Reducing the risk of stroke in elderly patients with non-valvular atrial fibrillation: a practical guide for clinicians.

Non-valvular atrial fibrillation (NVAF) significantly contributes to the burden of stroke, particularly in elderly patients. The challenge of optimizing anticoagulation therapy is balancing efficacy and bleeding risk, especially as the same patients at high risk of stroke also tend to be at high risk of bleeding. Treating the elderly patient with NVAF presents special challenges because of their heightened risk for both stroke and bleeding. Despite clinical trial data and evidence-based guidelines, surveys indicate that physicians underuse anticoagulation in older patients for reasons that include overemphasis of bleeding risk, particularly with the increased risk of falling, at the cost of thromboembolic risk. Clinical trial data are now available, and real-world data are emerging, to illustrate the relative merits of the non-vitamin K antagonist oral anticoagulants compared with conventional anticoagulation in the treatment of elderly patients with this condition, and to suggest some subgroups of older patients who may be more suitable candidates for particular agents. Care of elderly patients with NVAF is often complicated by factors including risk of falling, adherence, health literacy, cognitive function, adverse effects, and involvement of caregivers, as well as other factors including the patient–provider relationship and logistical barriers to obtaining medication. Thus, conversations between clinicians and patients, as well as shared decision making, are important. In addition, elderly patients often suffer from comorbidities including hypertension, coronary heart disease, diabetes mellitus, COPD, and/or heart failure, which necessitate the use of multiple concomitant medications, increasing the risk of drug/drug interactions. This review provides an overview of clinical trial data on the use of non-vitamin K anticoagulant agents in elderly populations, and serves as a practical resource for the management of NVAF in the elderly patient.

Predictors of polypharmacy and off-label prescribing of psychotropic medications: a national survey of child and adolescent psychiatrists.

We employed a national survey of child psychiatrists to examine typical prescribing practices for children with anxiety, depression, and disruptive behavior disorders. We examined the extent to which polypharmacy and off-label prescribing occur in routine practice and the degree to which child characteristics, child psychiatrist characteristics, and medication availability may influence these prescribing practices. We found that child psychiatrists most often prescribed medications that were on-label according to U.S. Food and Drug Administration (FDA) guidelines, and that they were progressively less likely to choose medications with partial approval (i.e., medications having pediatric approval but not for the patient's age or problem type), and then medications with no pediatric approval. We also found that prescribing multiple concomitant medications was the norm. We employed best subsets regression to determine the best theoretically relevant predictors to explain polypharmacy and off-label prescribing and found that the best fitting model only included number of child diagnoses. These findings suggest that comorbidity is an important issue in the pharmacotherapy of children with mental health disorders and one that must be addressed in future clinical trials.

Avoiding idiosyncratic DILI: Two is better than one

Avoiding idiosyncratic DILI: Two is better than one

How to Integrate Multiple Comorbidities in Guideline Development

Professional societies, like many other organizations around the world, have recognized the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the 10th of a series of 14 articles that were prepared to advise guideline developers in respiratory and other diseases. This article deals with how multiple comorbidities (co-existing chronic conditions) may be more effectively integrated into guidelines. In this review we addressed the following topics and questions using chronic obstructive pulmonary disease (COPD) as an example. (1) How important are multiple comorbidities for guidelines? (2) How have other organizations involved in the development of guidelines for single chronic disease approached the problem of multiple comorbidities? (3) What are the implications of multiple comorbidities for pharmacological treatment? (4) What are the potential changes induced by multiple comorbidities in guidelines? (5) What are the implications of considering a population of older patients with multiple comorbidities in designing clinical trials? Our conclusions are based on available evidence from the published literature, experience from guideline developers, and workshop discussions. We did not attempt to examine all Clinical Practice Guidelines (CPGs) and relevant literature. Instead, we selected CPGs generated by prominent professional organizations and relevant literature published in widely read journals, which are likely to have a high impact on clinical practice. A widening gap exists between the reality of the care of patients with multiple chronic conditions and the practical clinical recommendations driven by CPGs focused on a single disease, such as COPD. Guideline development panels should aim for multidisciplinary representation, especially when contemplating recommendations for individuals aged 65 years or older (who often have multiple comorbidities), and should evaluate the quality of evidence and the strength of recommendations targeted at this population. A priority area for research should be to assess the effect of multiple concomitant medications and assess how their combined effects are altered by genetic, physiological, disease-related, and other factors. One step that should be implemented immediately would be for existing COPD guidelines to add new sections to address the impact of multiple comorbidities on screening, diagnosis, prevention, and management recommendations. Research should focus on the possible interaction of multiple medications. Furthermore, genetic, physiological, disease-related, and other factors that may influence the directness (applicability) of the evidence for the target population in clinical practice guidelines should be examined.

Beers revised: Drugs not to use in older adults

Older adults are generally characterized as patients who may be at an increased risk for adverse drug events because of altered pharmacokinetics, increased exposure to multiple concomitant medications, and comorbid conditions. In 1991, Mark Beers, MD, and colleagues published criteria listing "potentially inappropriate medications" for older patients. Updates to these criteria were subsequently published in 1997, 2003, and earlier this year in the Journal of the American Geriatrics Society . The revised 2012 version heralds a new partnership between an interdisciplinary panel of experts and the American Geriatrics Society.

P3-018 - Concomitant Polypharmacy is Associated with Irinotecan-Induced Adverse Drug Reactions in Patients with Cancer

ABSTRACT Background Patients with cancer are often given chemotherapeutic agents concurrently with other medications to treat comorbidity. The practical effects of concomitant medicines, especially polypharmacy, on adverse drug reactions induced by irinotecan-based chemotherapy were not well documented. Methods Associations of adverse drug reactions related to irinotecan monotherapy or a combination of irinotecan, 5-fluorouracil, and l-leucovorin (FOLFIRI) with concomitant medicines used to treat comorbidity were retrospectively investigated in Japanese patients with cancer. Concomitant medications were defined as therapeutic drugs which were given to manage comorbid conditions besides cancer, and those continuously administered at least from the last visit before the start of irinotecan-based chemotherapy until after day 1 of the chemotherapy. Results Among the 172 patients, 118 received concomitant medications. Almost all concomitant medications were continuously administered from the last visit before starting irinotecan-containing chemotherapy to until the end of the first cycle. Twenty one patients had grade 4 neutropenia and/or grade 3 or 4 diarrhea. Univariate and multivariate analyses revealed that concomitant medications were significantly associated with irinotecan-related severe neutropenia and/or diarrhea (P = 0.023 and 0.044). Multiple concomitant medications were significantly related to severe irinotecan-related toxicity in patients given monotherapy or FOLFIRI (P = 0.01). The incidence of severe irinotecan-related toxicities increased in parallel to the number of concomitant medications. Conclusion We thus demonstrated that multiple concomitant medications were significantly associated with irinotecan-related severe toxicity in patients with cancer who received irinotecan-based chemotherapy, indicating that polypharmacy must be effectively managed to decrease the risk of adverse drug reactions.

Concomitant polypharmacy is associated with irinotecan-related adverse drug reactions in patients with cancer

Patients with cancer often receive chemotherapeutic agents concurrently with other medications to treat comorbidity. The practical effects of concomitant medications, especially polypharmacy, on adverse drug reactions related to irinotecan-based chemotherapy are not well documented. Associations of adverse drug reactions related to irinotecan monotherapy or a combination of irinotecan, 5-fluorouracil, and L-leucovorin (FOLFIRI) with concomitant medicines used to treat comorbidity were retrospectively investigated in Japanese patients with cancer. Of the 172 patients, 118 received concomitant medications. Twenty-one patients had grade 4 neutropenia and/or grade 3 or 4 diarrhea. Univariate and multivariate analyses revealed that concomitant medications were significantly associated with irinotecan-related severe neutropenia and/or diarrhea (P = 0.023 and 0.044). Multiple concomitant medications were significantly related to severe irinotecan-related toxicity in patients given monotherapy or FOLFIRI (P = 0.01). The incidence of severe irinotecan-related toxicities increased in parallel with the number of concomitant medications. We found that multiple concomitant medicines were significantly associated with severe irinotecan-related toxicity, indicating that polypharmacy must be effectively managed to decrease the risk of adverse drug reactions in patients with cancer who received irinotecan-based chemotherapy.

Demographic Characteristics and Patterns of Medication in Atrial Fibrillation Patients in South West Ontario: Insights from a Large Primary Care Database.

Background: Information about current practice in primary care-based management of atrial fibrillation (AF) can help to improve care quality. Purpose: To assess the epidemiology of AF and current patterns of treatment in order to identify therapeutic trends and aspects of current practice that may allow for care-gap identification. Methods: We scrutinized the anonymized records of the South Western Ontario database (SWO) collected between July 2002 and October 2008 for information about the characteristics and management of AF patients. Results: From a population of ~168,000 patients we identified 4922 patients with a diagnosis of AF (2.9%). The recorded prevalence of AF increased with age, from <2% at age <60 years to 6% in the age range 71-75 years and 10% at age ≥81 years. AF patients were characterized by an unfavourable cardiovascular risk profile including widespread hypertension (54% of all cases), coronary artery disease (37%) and heart failure (21%), many cases of which were advanced (New York Heart Association class III or IV). Diabetes (22%) and dyslipidaemia (31%) were also widely prevalent. The most frequently prescribed anti-arrhythmic drugs (AADs) were sotolol (n=798), amiodarone (n=712) and propafenone (n=451). Recorded use of flecainide was relatively low (n=175). Rate control-agents were being prescribed for 1838 patients, beta-blockers for 1311 patients and calcium channel blockers (CCBs) for 784 patients. Use of anticoagulants was higher among patients assigned to AADs than among those assigned to rate-control drugs (>25% vs. ~10%). Overall prescription rates for other concomitant medications were >50% for ACE inhibitors/ARBs, 30-35% for statins and beta-blockers, and 27-29% for diuretics, digoxin and CCBs. Conclusions: These Canadian patients with AF were relatively elderly and had multiple concomitant cardiovascular conditions and medications.